The two extremes of Hansen’s disease—Different manifestations of leprosy and their biological consequences in an Avar Age (late 7th century CE) osteoarchaeological series of the Duna-Tisza Interfluve (Kiskundorozsma–Daruhalom-dűlő II, Hungary)

To give an insight into the different manifestations of leprosy and their biological consequences in the Avar Age of the Hungarian Duna-Tisza Interfluve, two cases from the 7th-century-CE osteoarchaeological series of Kiskundorozsma–Daruhalom-dűlő II (Hungary; n = 94) were investigated. Based on the macromorphology of the bony changes indicative of Hansen’s disease, KD271 (a middle-aged male) and KD520 (a middle-aged female) represent the two extremes of leprosy. KD271 appears to have an advanced-stage, long-standing near-lepromatous or lepromatous form of the disease, affecting not only the rhinomaxillary region but also both upper and lower limbs. This has led to severe deformation and disfigurement of the involved anatomical areas of the skeleton, resulting in his inability to perform the basic activities of daily living, such as eating, drinking, grasping, standing or walking. The skeleton of KD520 shows no rhinomaxillary lesions and indicates the other extreme of leprosy, a near-tuberculoid or tuberculoid form of the disease. As in KD271, Hansen’s disease has resulted in disfigurement and disability of both of the lower limbs of KD520; and thus, the middle-aged female would have experienced difficulties in standing, walking, and conducting occupational physical activities. KD271 and KD520 are amongst the very few published cases with leprosy from the Avar Age of the Hungarian Duna-Tisza Interfluve, and the only examples with detailed macromorphological description and differential diagnoses of the observed leprous bony changes. The cases of these two severely disabled individuals, especially of KD271 –who would have required regular and substantial care from others to survive–imply that in the Avar Age community of Kiskundorozsma–Daruhalom-dűlő II there was a willingness to care for people in need.

From the four medical conditions collectively referred to as treponematoses, pinta, bejel, yaws, and syphilis, the three latter ones can affect the bones in their advanced stages [1,[4][5][6]. Bejel, yaws, and syphilis are caused by three different subspecies of the bacterium Treponema pallidum [6][7]. As pinta never involves the skeleton [1,[4][5][6], it can be ruled out as a diagnostic option in KD271. Bejel and yaws are limited to particular geographical regions of the world: arid, subtropical and humid, tropical areas, respectively [1,[4][5]8]. Therefore, both bejel and yaws can be excluded in the differential diagnosis of KD271. Acquired syphilis tends to affect the bones of the skull vault and of the rhinomaxillary region of the face in its tertiary stage [1,[4][5]. In the latter area, the nasal bones (not observable in our case), the bony nasal septum, the maxillary palatine process, the nasal conchae, and the lateral walls of the maxillary sinuses are the most frequently involved sites, whereas the anterior nasal spine and the maxillary alveolar process are usually spared [4][5][9][10]. Although acquired syphilis cannot be completely rejected as a diagnostic option in KD271, as the earliest identified cases of the disease from the present-day territory of Hungary derive from the end of the 15 th century CE [11], it is unlikely that acquired syphilis resulted in the development of the bony changes observed in the rhinomaxillary region of the face of KD271. Tuberculosis, caused by members of the Mycobacterium tuberculosis complex, is primarily a pulmonary disease; nevertheless, it can affect any part of the human body, including the skin [1][2]4,12]. Tuberculosis of the facial skin and soft tissues, facial lupus vulgaris, is a rare extra-pulmonary manifestation of the disease [12][13][14]. Although long-standing facial lupus vulgaris can result in secondary involvement of the underlying bone, the maxillary alveolar process is rarely affected by tuberculosis [2,10].
Actinomycosis, caused by Actinomyces spp., is a rare medical condition, and actinomycotic involvement of the skeleton is even more uncommon [1,[4][5][15][16]. In the skull, the mandible (unchanged in our case) presents the most frequently affected site, whereas the maxilla is an extremely rare localisation of actinomycosis [1,[4][5]16]. Based on their localisation preference and rarity, facial lupus vulgaris and actinomycosis seem to be less likely to be responsible for the formation of the bony changes detected in the rhinomaxillary region of the face of KD271.

Aspergillosis due to Aspergillus spp. is a sporadic systemic fungal infection with
worldwide distribution that can occasionally affect the skeleton [1,[17][18][19]. If the skull is involved in aspergillosis, the nasal cavity, and the paranasal sinuses and their walls are primarily affected with eventual extension of the infection into the orbits (not changed in our case) [1,17,19]. Similar to aspergillosis, mucormycosis is a rare systemic infection with worldwide distribution that is caused by fungi belonging to the Mucoraceae family of the Mucorales order [1,17]. In the most common form of the disease, rhinocerebral mucormycosis, the infection can extend into the bones [1,17,[19][20][21]. It spreads in the nasal cavity and paranasal sinuses with subsequent development of sinusitis; from here, the disease frequently progresses into the orbits (not in our case) [1,17,[19][20][21]. In mucormycosis, usually only one of the maxillary sinuses is affected with consequent perforation of the corresponding maxillary palatine process [1,17,19].
Based on the above, aspergillosis and mucormycosis can be excluded in the differential diagnosis of KD271.
Sarcoidosis is an uncommon systemic granulomatous disease of unknown aetiology that generally occurs in adults between 25 and 40 years of age and appears to have a predilection for individuals of African descent [17,19,[22][23][24]. Sarcoidosis rarely (~1%) affects the nasal mucosa and consequently the bones of the rhinomaxillary region of the face [12,17,25]. When it does, the nasal bones (not observable in our case) are the primary site of involvement, whereas the anterior nasal spine and the maxilla are not typical localisations of the disease [2,19].
Considering the racial predilection, age and localisation preference, and rarity of sarcoidosis, this medical condition can be ruled out with high certainty as a diagnostic option in KD271.